Drug abuse is a pervasive problem in modern society. The most abusable and addictive drugs are those which have fast onsets and short durations of action. Cocaine, for example, has an onset of action on the order of seconds and of synaptic dopamine and this is associated with feelings of euphoria and well being. While the immediate, short term effect of cocaine is to increase synaptic levels of dopamine, chronic use of cocaine may result in depleted levels of synaptic dopamine in the absence of cocaine. This has been associated with ahedonia and chronic cocaine craving upon cessation of cocaine use.
One strategy for treating cocaine abusers is to administer an alternative dopamine reuptake blocker which will raise synaptic levels of dopamine. Known methods for raising reduced levels of synaptic dopamine and thus, reducing the craving for cocaine, include the use of compounds that block dopamine reuptake. (Rosenzweig-Lipson et al., Psychopharmacology 10:186 (1992)). However, even these dopamine reuptake blockers are limited to a duration of between about two and four days (Rosenzweig-Lipson et al., Psychopharmacology 10:186 (1992)). Even a duration of two to four days requires a relatively regimented schedule for patients, who, because of their affliction, may not adhere to the prescribed dosages.
There is a continuing need for new medications for the treatment of cocaine abuse. Further, drugs which block the reuptake of dopamine are also believed to have other potential utilities such as for the treatment of attention deficit hyperactivity disorder and Parkinson's disease.